RESUMO
Sperm parameters are known to be impaired in men with sickle cell disease (SCD). Although treatment with hydroxyurea (HU) has an impact on sperm quality, sperm preservation is impossible before puberty. This study's primary objective was to analyze and compare sperm parameters in male patients with SCD exposed (or not) to HU before puberty. Twenty-six sperm samples from 15 patients (median age, 17 years; range, 16-23) treated with HU during childhood were compared with 46 samples from 23 HU-naïve patients (20 years; 16-24). The median age at HU initiation was 6 years (1-14 years), the median duration of HU treatment was 4 years (0.5-10), and the mean dose of HU was 22.4 ± 3.7 mg/kg per day. Although we observed substantial quantitative and qualitative semen abnormalities in all patients, there were no significant differences in semen volume, sperm concentration, total sperm count, or spermatozoa motility, morphology, and vitality between the HU-exposed and HU-naïve groups. At the time of the semen analysis, 100% of the patients in the HU-exposed group and 52% of the patients in the HU-naïve group received transfusion therapy. The specific effect of HU on spermatogenesis in very young infants and the putative value of transfusion for reversing the toxicity of HU warrant further investigation.
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Hidroxiureia/efeitos adversos , Infertilidade Masculina/induzido quimicamente , Puberdade , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/etiologia , Adolescente , Fatores Etários , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Anemia Falciforme/terapia , Antidrepanocíticos/administração & dosagem , Antidrepanocíticos/uso terapêutico , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/etiologia , Transfusão de Sangue , Criança , Pré-Escolar , Terapia Combinada , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/uso terapêutico , Lactente , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Adulto JovemRESUMO
Sickle cell disease is the most frequent genetic disease in France, concerning 400 newborns each year. The management of these Afro-Caribbean patients requires frequent transfusions from Caucasian donors. Due to important erythroid antigenic differences between Caucasian and African, the prevalence of allo-immunization is high in this population with a risk of transfusional impasse. Allogeneic stem cell transplantation is the only curative treatment for this disease and the replacement of red cells and lymphocytes of the sickle cell patient by those of the donor can also resolve the transfusional impasse. However, a close consultation between physicians from the blood bank and transplantation unit will be required for the choice of conditioning regimen and GvH prophylaxis in order to ensure the transition from a mixed chimerism to the full donor curative graft.
Assuntos
Anemia Falciforme/terapia , Transfusão de Sangue , Transplante de Células-Tronco Hematopoéticas , Anemia Falciforme/genética , Anemia Falciforme/imunologia , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Ensaios Clínicos como Assunto , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Humanos , Imunização , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Reação Transfusional/prevenção & controle , Condicionamento Pré-TransplanteRESUMO
AIMS: Perform an agreement and reproducibility study of the estimation of iron overload in highly transfused pediatric patients comparing R2* relaxometry (R2*=1000/T2*) to the reference technique liver/muscle signal intensity ratio (SIR). PATIENTS AND METHODS: Ninety-two MRI were performed in 68 children who were mainly transfused for sickle cell disease, mean age 9.9 years old. The examination included six sequences for the SIR protocol and a single multiecho T2* sequence. R2* relaxometry was measured by two radiologists independently, either by a region of interest (ROI) in the right liver, or an outline of the whole liver. Hepatic iron load was determined by the Wood formula (Fe mg/g=R2*×0.0254+0.202). The validity of R2* relaxometry compared to SIR was evaluated by the coefficient of variation and the quadratic weighted Kappa value. RESULTS: The correlation between R2* relaxometry and SIR was very good with a Pearson coefficient of 0.89 and a coefficient of variation of 17.3%. The inter- and intraobserver reproducibility of the measurement of R2* relaxometry by ROI and whole liver mapping was excellent. However, we observed a common positive variation of one class between SIR and R2* relaxometry, with higher hepatic iron content values with SIR than with R2* relaxometry. CONCLUSION: Hepatic iron content can be rapidly and precisely estimated on MRI by multiecho gradient-echo sequences.
Assuntos
Transfusão de Sangue , Sobrecarga de Ferro/diagnóstico , Hepatopatias/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adolescente , Anemia Falciforme/terapia , Criança , Pré-Escolar , Humanos , Sobrecarga de Ferro/complicações , Fígado/patologia , Hepatopatias/complicações , Músculo Esquelético/patologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Cerebral vascular disease in children with sickle cell disease is characterized by progressive stenosis of large arteries of the skull base, which can be detected sensitively, specifically and unexpensively by transcranial Doppler. Because sickle cell disease is responsible for basal high velocities, criteria used for diagnosis of stenosis are different than those used in non sickled children and moreover in adults. Mean velocity higher than 2 meters per second is predictive of a 40% risk for stroke in the three following years, but transfusion program maintaining hemoglobin S under 30%, reduces the risk to 2%. It is important to test each child with sickle cell disease by the age of one or two years, in order to detect cerebral vasculopathy before overt stroke and its residual deficits and to initiate appropriate treatment
Assuntos
Anemia Falciforme/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Adulto , Transtornos Cerebrovasculares/etiologia , Criança , HumanosRESUMO
It is thought that an increase in the adhesion of circulating reticulocytes to the vascular endothelium may initiate the vascular occlusion underlying the painful crises and organ failures typical of sickle cell disease (SCD). At least 2 receptors, usually present on reticulocytes, seem to be involved in this adhesion process: glycoprotein CD36 (glycoprotein IV) and integrin alpha(4)beta(1) (very late activation antigen--4). Recently, a high frequency of the platelet CD36--deficient phenotype was reported in black Africans. The frequency of this deficiency was similar in subjects with and without SCD. The role of CD36 in vaso-occlusion was then investigated by comparing the clinical course in 2 groups of black Africans homozygous for hemoglobin S, with and without CD36 deficiency, but similar in age, sex, geographical origin, number of alpha-globin genes, and beta-globin gene haplotype. Flow cytometry showed that CD36 was absent from the circulating red blood cells and reticulocytes of platelet CD36--deficient individuals but present on those from patients with normal platelet CD36 expression, and that alpha(4)beta(1) integrin levels were similar on the reticulocytes of the 2 groups. Neither clinical severity, as evaluated by the frequency and characteristics of vaso-occlusive events, nor biological data differed significantly in the 2 groups of patients. Finally, although CD36 has been suggested to play a critical role in the pathogenesis of vaso-occlusion, this study, despite including only a small number of patients, supports the idea that the modulation of expression of a single type of adhesion molecule is insufficient to counteract the pathological process leading to vaso-occlusion in SCD patients. (Blood. 2001;98:966-971)
Assuntos
Anemia Falciforme/sangue , Antígenos CD36/biossíntese , Eritrócitos/química , Reticulócitos/metabolismo , Adolescente , Adulto , Anemia Falciforme/diagnóstico , Anemia Falciforme/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Análise por Pareamento , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n = 156) (Wechsler Intelligence tests WISC-III, WIPPSI-R), which were also performed in 76 sibling controls (5 to 15 years old). Among the 173 patients with sickle cell disease (155 homozygous for hemoglobin SS, 8 sickle cell beta0 thalassemia, 3 sickle cell beta+ thalassemia, 7 sickle cell hemoglobin C disease SC), 12 (6.9%) had a history of overt stroke, and the incidence of abnormal transcranial Doppler ultrasonography (defined as mean middle cerebral artery velocity > 200 cm/sec or absent) was 8.4% in the overall study population and 9.6% in patients with homozygous sickle cell anemia The silent stroke rate was 15%. Significantly impaired cognitive functioning was observed in sickle cell disease patients with a history of stroke (Performance IQ and Full Scale IQ), but also in patients with silent strokes (Similarities, Vocabulary, and Verbal Comprehension). However, infarcts on magnetic resonance imaging were not the only factors of cognitive deficit: Verbal IQ, Performance IQ, and Full Scale IQ were strongly impaired in patients with severe chronic anemia (hematocrit < or = 20%) and in those with thrombocytosis (platelets > 500 x 10(9)/L). Multivariate logistic regression analysis showed that abnormal magnetic resonance imaging (odds ratio [OR] = 2.76) (P = .047), hematocrit < or =20% (OR = 5.85) (P = .005), and platelets > 500 x 10(9)/L (OR = 3.99) (P = .004) were independent factors of cognitive deficiency (Full Scale IQ < 75) in sickle cell disease patients. The unfavorable effect of low hematocrit has already been suggested, but this is the first report concerning an effect of thrombocytosis and showing that silent stroke alone is not a factor of cognitive deficit when not associated with low hematocrit or thrombocytosis. The effect of hydroxyurea, which is known to increase hematocrit and decrease platelet count, on cognitive functioning of sickle cell patients should be evaluated prospectively.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/psicologia , Transtornos Cognitivos/etiologia , Inteligência , Acidente Vascular Cerebral/psicologia , Adolescente , Anemia/psicologia , Criança , Pré-Escolar , Feminino , França , Hematócrito , Humanos , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Contagem de Plaquetas , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Trombocitose/psicologia , Ultrassonografia Doppler TranscranianaRESUMO
A novel HLA-B*39 variant, found in an African patient with sickle cell anemia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR-SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B*3916. It differs from HLA-B*3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at codon 96 of alpha(2) domain, a conserved position among HLA class I alleles. cDNA sequence analysis further revealed the presence of both normally and abnormally spliced mRNA species in established cell lines. The abnormal species correspond to partial truncation of exon 3 presumably due to the nucleotide change in exon 3, which constitutes a new consensus acceptor splice site within this exon. We postulate that the observed blank is essentially the consequence of qualitative change in a critical region of this novel antigen as abnormal mRNA species are relatively less abundant than normal species. Because the residue 96 of the HLA class I heavy chain is directly involved in interaction with alpha(2)m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and consequently could affect the serological specificity of B*3916, or its expression or both.
Assuntos
Antígenos HLA-B/genética , Mutação , Splicing de RNA , Sequência de Aminoácidos , Sequência de Bases , Feminino , Antígeno HLA-B39 , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fases de Leitura , Homologia de Sequência do Ácido NucleicoRESUMO
Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)
Assuntos
Anemia Falciforme/terapia , Transplante de Medula Óssea , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Estatura , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Glândulas Endócrinas/metabolismo , Feminino , Seguimentos , Humanos , Pulmão/fisiologia , Masculino , Fatores de Tempo , Doadores de TecidosAssuntos
Anemia Falciforme/diagnóstico , Triagem Neonatal , Feminino , França , Humanos , Recém-Nascido , Masculino , População UrbanaRESUMO
To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome). We have identified 14 new heterozygous Fas mutations. Analysis of patients and families allow us to further dissect this syndrome with regards to the relationship between Fas mutations, inheritance pattern, and phenotype as observed on long-term follow-up. In vitro studies show that lymphocytes from all Fas mutant carriers exhibit a Fas-antibody-induced apoptosis defect. However, among the 8 inherited mutations, 4 of 4 Fas missense mutations were associated with high clinical penetrance, whereas 3 of 4 mutations leading to a truncated Fas product were associated with variable clinical penetrance. This suggests that a second defect, in another yet undefined factor involved in apoptosis and/or lymphoproliferation control, is necessary to induce full clinical expression of the disease. These results also indicate that the currently available antibody-mediated in vitro apoptosis assay does not necessarily reflect the in vivo ability of abnormal Fas molecules to trigger lymphocyte death. In addition, we found that lymphoproliferative manifestations resolved with age, whereas immunological disorders [ie, hypergammaglobulinemia and detection of TcR alphabeta(+) CD4(-) CD8(-) lymphocytes] persisted. This observation suggests that Fas-mediated apoptosis plays a more important role in lymphocyte homeostasis in early childhood than later on in life.
Assuntos
Doenças Autoimunes/genética , Transtornos Linfoproliferativos/genética , Receptor fas/genética , Adolescente , Adulto , Fatores Etários , Substituição de Aminoácidos , Apoptose , Doenças Autoimunes/imunologia , Criança , Éxons/genética , Feminino , Seguimentos , Genes Dominantes , Heterogeneidade Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Hipergamaglobulinemia/etiologia , Hiperesplenismo/etiologia , Hiperesplenismo/cirurgia , Lactente , Transtornos Linfoproliferativos/imunologia , Masculino , Mutação Puntual , Esplenectomia , Esplenomegalia/etiologia , Esplenomegalia/cirurgia , Linfócitos T/química , Linfócitos T/patologia , Uveíte/etiologiaRESUMO
AIM: To evaluate the tolerance of hydroxyurea in children affected with sickle cell disease. DESIGN: Questionnaire study of French physicians likely to treat patients with sickle cell disease. Data were collected on 101 children with sickle cell disease, treated for a median of 22 months, 36 of whom were treated for more than three years. 13 children were younger than 5 years of age at inclusion. RESULTS: Hydroxyurea was stopped for medical reasons in 11 patients: 6 failures, 1 pregnancy, 1 cutaneous rash, 1 leg ulcer, 1 lupus. Acute lymphoblastic leukaemia occurred in a girl treated for 1.5 months with hydroxyurea, this short interval arguing against a causative association. One 17 year old boy had paraparesis after 8 years of treatment. CONCLUSIONS: No major short or medium term toxicity was related to hydroxyurea in this cohort of 101 children. However, the number of children treated for more than 3 years is too few to make firm conclusions on the long term tolerance of this drug.
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Hidroxiureia/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Toxidermias/etiologia , Feminino , Humanos , Úlcera da Perna/induzido quimicamente , Masculino , Gravidez , Complicações Hematológicas na Gravidez , Falha de TratamentoRESUMO
Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (=6.65%). Restriction enzyme analysis of the V9 genome revealed that this genetic divergence extended beyond the amplified region. Interestingly, serological tests failed to demonstrate a response characteristic of acute B19 infection. V9 could be a new erythrovirus, and new diagnostic tests are needed for its detection.
Assuntos
Anemia Aplástica/virologia , Erythrovirus/genética , Erythrovirus/isolamento & purificação , Sequência de Aminoácidos , Sequência de Bases , Erythrovirus/classificação , Genoma Viral , Humanos , Dados de Sequência Molecular , FilogeniaRESUMO
Since 1988, 34 pediatric patients with severe sickle cell disease have received bone marrow transplantation (BMT) from HLA-identical siblings in France. After 1992, documentation of the favorable effect of hydroxyurea therapy on the frequency of vasoocclusive crisis (VOC) left a history of stroke (n = 16) as the main indication for BMT. Among patients treated by genoidentical BMT, 85% were cured and 9% died. All deaths were due to severe graft-versus-host disease. The rejection rate fell from 25% to 5% after addition of ATG to the conditioning regimen. BMT reversed some sickle cell disease-related abnormalities: splenic function improved and some cases of osteonecrosis showed a favorable course. Fifteen of 16 patients with a history of stroke showed no stroke recurrence after BMT, and arterial stenoses improved. BMT should be offered to sickle cell anemia patients with a history of stroke if a genoidentical donor is available. To prevent stroke-related residual impairment and transfusion-related complications, BMT should be considered early in patients with Doppler or MRI evidence of silent stroke associated with cognitive function impairment, failure to respond to hydroxyurea therapy (frequent VOCs, severe anemia and thrombocytosis, multifocal osteonecrosis), or polyerythroalloimmunization. Storage of frozen of cord blood samples from siblings should be considered.
Assuntos
Anemia Falciforme/terapia , Transplante de Medula Óssea , Anemia Falciforme/mortalidade , Antidrepanocíticos/uso terapêutico , Transfusão de Sangue , Butiratos/uso terapêutico , Criança , Hemoglobina Fetal/biossíntese , Rejeição de Enxerto , Humanos , Hidroxiureia/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B/imunologia , Imunossupressores/efeitos adversos , Ativação Viral , Adolescente , Adulto , Criança , Feminino , Anticorpos Anti-Hepatite B/análise , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
Patients with beta-thalassemia (Hbeta th) and sickle cell anemia (SCA) can be treated with bone marrow transplantation. Stem cells from cord blood have several theoretical advantages, however, the place of cord blood transplant for hemoglobinopathies has not yet been established. We report here the EUROCORD experience of 10 patients (Hbeta th = 7, SCA = 3) transplanted with related cord blood.
Assuntos
Anemia Falciforme/terapia , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas , Talassemia beta/terapia , Antineoplásicos Alquilantes/uso terapêutico , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Metotrexato/uso terapêutico , Estudos Prospectivos , Tiotepa/uso terapêutico , Resultado do TratamentoRESUMO
Eurocord Transplant has established a registry for studying results of cord blood transplant. We have analyzed 78 patients who have received a related CBT between October 1988 and December 1996. The median follow-up time was 29 months (1-99). The median age was 5 years (0.2-20), median weight 19 kg (5-50). Forty-six patients had a malignant disease: 32 acute leukemia (AL), six chronic myeloid leukemia (CML), four myelodysplastic syndrome, two neuroblastoma and two non-Hodgkin lymphoma. Thirty-two patients were transplanted for non-malignant diseases including 17 bone marrow failure syndromes (BMFS), three sickle cell anemia, five thalassemia and seven inborn errors. The donor was an HLA-identical sibling in 60 cases and an HLA-mismatched donor in 18 cases. As conditioning, 36 patients received irradiation and 40 patients received associated busulfan-containing regimens. GVHD prophylaxis consisted of CsA alone in 36 cases, CsA associated with prednisone in eight cases, CsA, methotrexate (Mtx) with or without prednisone in 28 cases and CsA with monoclonal antibody or ATG in four cases. The median number of nucleated cells (NC) infused/kg was 3.9 x 10(7) (0.7-15). One-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA-matched CBT and 50% in mismatched CBT (P < 0.001). Neutrophil engraftment was associated with age <6 years (P = 0.02) and weight <20 kg (P = 0.02). It was 73% in patients receiving <3.7 x 10(7) nucleated cells (NC) infused/kg and 85% in patients receiving more (P = 0.06). Favorable factors for platelets engraftment were age <6 years (P = 0.03), weight <20 kg (P = 0.002) and HLA identity (P < 0.0001). Related cord blood transplantation offers a good alternative to BMT. Theses results are in favor of freezing cord blood in families in whom a transplant might be indicated.